| Eligibility |
Inclusion Criteria:
1. Age = 18 years of age at time of consent
2. Histologically confirmed invasive breast carcinoma documented by core needle biopsy or
incisional biopsy (excisional biopsy is not allowed). AJCC 8th edition clinical stage
T1b-T3/N0-N3/M0 by physical exam or radiologic studies
3. Must be candidates for curative surgical resection
4. Have an FFPE diagnostic core biopsy specimen available that is determined by the study
pathologist to be adequate for planned analyses
5. Definitive surgical excision of the primary breast tumor (either partial mastectomy or
total mastectomy) and ipsilateral axillary lymph node sampling (sentinel lymph node
biopsy or axillary dissection) is planned following completion of preoperative
chemotherapy.
6. Estrogen Receptor (ER)- and Progesterone Receptor (PR)-negative as determined by
immunohistochemistry (IHC), and Human Epidermal Growth Factor Receptor (HER)2-negative
(triple-negative) cancer of the breast
Triple-negative tumors are defined as:
- Less than or equal to 10% of tumor cells staining for ER and for PR by
immunohistochemistry (IHC)
- HER2-negative, as defined by ASCO/CAP guidelines55
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 30
days prior to study registration
8. Demonstrate adequate organ function as defined in the table below; all screening labs
to be obtained within 30 days prior to registration Hematological Leukocytes
=2,500/mm3 Platelet count = 100,000/mm3 Absolute Neutrophil Count (ANC) = 1,500/mm3
Hemoglobin (Hgb) = 9.0 g/dL Renal Creatinine/Calculated creatinine clearance (CrCl) Cr
< 1.5 x upper limit of normal (ULN) or CrCl = 50 mL/min using the Cockcroft-Gault
formula Hepatic Bilirubin Bilirubin = 1.5 × ULN. Subjects with Gilbert's syndrome may
have a bilirubin > 1.5 × ULN, if no evidence of biliary obstruction exists Aspartate
aminotransferase (AST) = 2.5 × ULN Alanine aminotransferase (ALT) = 2.5 × ULN
9. No evidence of distant metastases (M0 as per AJCC staging guidelines)
10. Provided written informed consent and HIPAA authorization for release of personal
health information, approved by an Institutional Review Board (IRB)
11. NOTE: HIPAA authorization may be included in the informed consent or obtained
separately
12. Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A
negative serum or urine pregnancy test is required within 14 days of study
registration. If the urine test cannot be confirmed as negative, a serum pregnancy
test will be required
13. Women of childbearing potential (WOCP) must be willing to use two effective methods of
birth control such as an oral, implantable, injectable, or transdermal hormonal
contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms,
sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total
abstinence for the course of the study until 120 days after the last dose of study
drug NOTE: Women are considered to be of childbearing potential unless they are
postmenopausal (=45 years of age and has not had menses for greater than 12
consecutive months or bilateral oophorectomy) or surgically sterile (bilateral tubal
ligation or hysterectomy) or not heterosexually active for the duration of the study
and at least 120 days after the last dose of study drug
14. As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study
Exclusion Criteria:
1. Active infection requiring systemic therapy
2. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study)
3. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic
therapy, radiotherapy directed towards the primary breast tumor and/or ipsilateral
axillary lymph nodes or investigational agents) with therapeutic intent for the
current breast cancer
4. Previous treatment with lenvatinib or any immune checkpoint inhibitor within the past
2 years
5. Treatment with any investigational drug within 14 days prior to registration or within
5 half-lives of the investigational product, whichever is longer
6. Major surgery within 14 days prior to registration or has not recovered from major
side effects of a major surgery (tumor biopsy and placement of an indwelling venous
access device are not considered major surgery)
7. Any prior or concurrent malignancy whose natural history or treatment has the
potential to interfere with the safety or efficacy assessment of this investigational
regimen, as determined by the treating Medical Oncologist.
8. Known history of AIDS (HIV testing is not mandatory). HIV-positive individuals on
active HARRT therapy with virologic suppression (defined as an HIV-1 RNA level below
the lower limit of detection of the assay used) within 90 days of study enrollment and
a CD4 cell count >500 cells/mm3 on the most recent determination are eligible for the
study
9. . Subjects with any of the following conditions:
- History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
abscess within 28 days prior to registration
- History of cerebrovascular accident (CVA) or transient ischemic attack within 6
months prior to registration
- History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to registration
- Symptomatic congestive heart failure (New York Heart Association III-IV) or
documented current left ventricular (LV) systolic dysfunction with left
ventricular ejection fraction (LVEF) <50% on most recent assessment of LV
function
- Clinically significant cardiac ventricular arrhythmias (e.g. sustained
ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g.
bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker
is in place
- Any concurrent severe and/or uncontrolled medical condition that would, in the
investigator's judgment, cause unacceptable safety risks, contraindicate subject
participation in the clinical study or compromise compliance with the protocol
10. Any condition that, in the opinion of the investigator, might jeopardize the safety of
the patient or interfere with protocol compliance
11. Any mental or medical condition that prevents the patient from giving informed consent
or participating in the trial
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